1,6-hexanediyl bismethacrylate

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Remarks:

Type of genotoxicity: gene mutation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1994-10-12 to 1994-10-28

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1995

Report date:

1995

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Version / remarks:

adopted 26 May 1983

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)

Version / remarks:

29 December 1992

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Tetramethylene dimethacrylate

EC Number:

218-218-1

EC Name:

Tetramethylene dimethacrylate

Cas Number:

2082-81-7

Molecular formula:

C12H18O4

IUPAC Name:

butane-1,4-diyl bis(2-methylacrylate)

Test material form:

other: liquid

Details on test material:

- Name of test material (as cited in study report): 1,4-Butanediol dimethacrylate

Method

Target gene:

his-locus

Species / strain

Species / strain / cell type:

S. typhimurium, other: S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 1538

Metabolic activation:

with and without

Metabolic activation system:

S9

Test concentrations with justification for top dose:

Experiment 1 (plate incorporation test): 33.3, 100.0, 333.3, 1000.0, 2500.0, 5000.0 µg/plate
Experiment 2 (pre-incubation test): 10.0, 33.3, 100.0, 333.3, 1000.0, 2500.0 µg/plate

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: DMSO
- Justification for choice of solvent/vehicle: solubility properties + relative nontoxicity to the bacteria

Controls

Controls 1

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

Positive controls:

yes

Positive control substance:

sodium azide

other: 4-nitro-o-phenylene-diamine

Remarks:

without metabolic activation

Controls 2

Positive controls:

yes

Positive control substance:

other: 2-aminoanthracene

Remarks:

with metabolic activation

Details on test system and experimental conditions:

METHOD OF APPLICATION: in agar (plate incorporation) and preincubation

DURATION
- Preincubation period: 60 minutes
- Exposure duration: at least 48 h

NUMBER OF EXPERIMENTS: 2 (one performed as pre-incubation assay, one as plate incorporation assay), 3 plates per concentration each

DETERMINATION OF CYTOTOXICITY
- Method: Toxicity of the test article may be evidenced by a reduction in the number of spontaneous revertants, a clearing of the bacterial background lawn, or by degree of survival of treated cultures.

OTHER:
automatic colony count with “AUTOCOUNT” (Artek systems, Biosys)

Evaluation criteria:

- corresponding background growth on negative control and test plates
- normal range of spontaneous revertants: TA1535 (10-29), TA 1537 (5-28), TA 1538 (12-37), TA 98 (15-57), TA 100 (77-189)
- test material is considered mutagenic if either a dose related and reproducible increase in revertant numbers or a significant and reproducible increase in revertant numbers for at least one test concentration in induced
- a significant increase in revertants means at least twice as high in TA 100 and a three times higher number in TA 1535, TA 1537, TA 1538, TA 89 compared to the negative control

Statistics:

no appropriate statistical method available

Results and discussion

Test results

Species / strain:

S. typhimurium, other: S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 1538

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

No substantial increases in revertant colony numbers of any of the five tester strains were observed following treatment with 1,4-Butanediol dimethacrylate at any dose level, either in the presence or absence of metabolie activation (S9 mix). There was also no tendency of higher mutation rates with increasing concentrations in the range below the generally acknowledged border of significance.

TEST-SPECIFIC CONFOUNDING FACTORS
- no data

RANGE-FINDING/SCREENING STUDIES:
- performed with 3.3, 10.0, 33.3, 100.0, 333.3, 1000.0, 2500.0 and 5000.0 µg/plate in TA 98 and TA 100
- normal background growth was observed up to 5000 µg/plate

COMPARISON WITH HISTORICAL CONTROL DATA:
controls were within the range of historical control data

ADDITIONAL INFORMATION ON CYTOTOXICITY:
- in the plate incorporation assay concentrations of 2500 µg/plate (without metabolic activation) and higher reduced the number of revertants in TA 1535, TA 1537 and TA 1538
- in the pre-incubation assay the number of revertants was reduced at concentrations of 1000 µg/plate (without metabolic activation) and higher in TA 1535 and TA 1537; at 2500 µg/plate (with metabolic activation) in TA 1537 and at 2500 µg/plate (without metabolic activation) in TA 1538

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
negative

In this study 1,4-BDDMA did not induce mutant colonies over background and is therefore considered non-mutagenic.

Executive summary:

In a reverse gene mutation assay in bacteria according to OECD guideline 471, adopted 26 May 1983, strains TA 1535, TA 1537, TA 98, TA 100 and TA 1538 of S. typhimurium were exposed to 1,4-BDDMA in DMSO at concentrations of 33.3, 100.0, 333.3, 1000.0, 2500.0, 5000.0 µg/plate in a plate incorporation assay and 10.0, 33.3, 100.0, 333.3, 1000.0, 2500.0 µg/plate in a pre-incubation assay in the presence and absence of mammalian metabolic activation (S9 mix).

1,4-BDDMA was tested up to cytotoxic concentrations. There was no evidence of induced mutant colonies over background.

The positive controls induced the appropriate responses in the corresponding strains.

This study is classified as acceptable and satisfies the requirement for Test Guideline OECD 471 for in vitro mutagenicity (bacterial reverse gene mutation) data.

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